Regulation by lithium of the antagonistic effect of cholecystokinin octapeptide on ohmefentanyl-induced antinociception

Abstract

The antagonistic effect on opioid analgesia of central cholecystokinin octapeptide (CCK-8) has been amply demonstrated by behavioral and electrophysiological studies, although the mechanisms of action remain obscure. Since the phosphatidylinositol (PI) system is known to be involved in CCK effects in pancreatic tissue, and lithium has been shown to interfere with PI turnover, we sought to investigate whether LiCl would block the antiopioid effect of CCK-8 in the CNS. Nociceptive thresholds were assessed by the latency of the tail flick response (TFL). Intrathecal injection (ith) of LiCl at 4 cumulative doses (1.25-25 mumol) produced no significant change in the baseline TFL, nor was the antinociceptive effect induced by ohmefentanyl (OMF, the mu-selective opioid agonist, 20 ng, ith) reversed by LiCl. However, OMF-induced antinociception was dose-dependently reversed by CCK-8 (1-16 ng, ith), which alone at 5 cumulative doses (1-20 ng) had no influence on TFL, and the reversal effect of CCK-8 could be readily antagonized by LiCl (0.6-20 mumol, ith). The results are interpreted to mean that the PI signal system may play an important role in mediating the antiopioid effect of CCK-8.